Can brain stimulation help with relearning movement after stroke?

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1 stroke.org.uk Final report summary Can brain stimulation help with relearning movement after stroke? The effect of transcranial direct current stimulation on motor learning after stroke PROJECT CODE: TSA 2013/09 PRINCIPAL INVESTIGATOR: PROFESSOR DI NEWHAM INSTITUTION: KING S COLLEGE LONDON

2 Why did we fund this research? Stroke is the leading cause of complex, adult disability, and even after rehabilitation many survivors are left dependent on others for normal activities of daily living 1,2. Rehabilitation of movement after stroke requires the re-learning of normal movement patterns that have been lost due to the brain injury 3, and this process is known as motor learning. There is some evidence that the rate at which motor learning takes place can be improved in healthy adults and well recovered chronic stroke survivors using a safe and painless, non-invasive brain stimulation technique called Transcranial Direct Current Stimulation (tdcs) 4-6. This is delivered through two plastic electrodes on the scalp for up to 20 minutes at a time. The positive electrode is called the anode and the negative one is called the cathode. Given the current evidence, it is unclear what the best position of the electrodes on the scalp is, in order to improve the rate of motor learning for stroke survivors One of the most important parts of the brain involved in motor learning is the motor cortex, which is present in the left and right sides (hemispheres) of the brain. It could be that placing the anode over the motor cortex affected by stroke works best. Alternatively, placing the cathode on the unaffected side may work best, or placing the electrodes over both the affected and unaffected sides of the motor cortex (bihemispheric stimulation) could produce the best results. Aims of the current study were to determine whether and how tdcs using different electrode placements on the scalp can: change the rate of motor learning in stroke survivors with one-sided arm and hand weakness; change the functional ability of the affected arm and hand and change the way the two sides of the brain communicate with each other. A final aim was to study whether the outcomes of the first three aims may be related. What did the researchers do? Twenty four stroke survivors with an average age of 60 years completed the study. All had their stroke at least three months before taking part in the study. Twelve had their right arm affected by stroke and the others their left. All participants attended five sessions. In the first session they were familiarised with the tasks and tests used in the study. These were a computerbased movement learning task; the Jebsen Taylor Test of hand function; and a test of the activity of the connections between the two sides of the brain. In the following four sessions, participants received 20 minutes of tdcs during the computer-based motor learning task; performed the Jebsen Taylor test before and after receiving tdcs; and at the end of each session underwent the test of activity of the two sides of the brain. In the computer based movement learning task, participants used their affected hand to move a computer mouse to targets on a computer screen which lit up in a repeating order. They were instructed to move the cursor out of a central (red) square to the lit target as quickly as possible. The time it took to move the cursor out of the central square and the speed and accuracy of movements to each of the targets was recorded, to see whether learning was improved with repetition, and with tdcs. The tdcs was delivered in different ways over the four sessions. Sham (dummy) tdcs was used as a control condition to determine the participants rate of learning and arm function without real brain stimulation. Anodal tdcs was delivered by placing the positive electrode over the stroke-affected hemisphere of the brain, in order to increase its activity. Cathodal tdcs was delivered by placing the negative electrode over the unaffected hemisphere, to decrease any over-activation. Bihemispheric tdcs delivered of both anodal and cathodal stimulation at the same time. It was hoped this study would inform the design of a larger clinical trial of how tdcs can best be used to improve the effects of rehabilitation after stroke. 2 Can brain stimulation help with relearning movement after stroke?

3 The Jebsen Taylor Test consists of a number of tasks of hand and arm function. Participants were timed both for how long it took them to complete the tasks before and after receiving tdcs in order to see whether function of the hand and arm improved. Activity of the connections between the two sides of the brain was measured with a different type of brain stimulation, called transcranial magnetic stimulation (TMS). What did the researchers find? These findings provide evidence that stimulation to increase activity of the affected hemisphere, and also that to decrease activity of the unaffected one, are effective when used separately. However bihemispheric stimulation does not provide additional benefit and in fact provides no benefit at all. This has implications for the design of future clinical trials to test the effect of tdcs in combination with physiotherapy after stroke. Findings from this study were published in the journal Disability & Rehabilitation in Although performance on the computer based motor learning task improved over the course of a session, it was not affected by the use of tdcs, regardless of the electrode arrangement. The time taken to perform the tasks of the Jebsen Test was reduced (improved) after participants received real tdcs in comparison with the sham version. This was dependent upon the electrode arrangement, with significant improvements after anodal (over the affected motor cortex) or cathodal tdcs (over the unaffected motor cortex) but not with bihemispheric tdcs. Hence anodal stimulation on the side of the brain affected by stroke, and cathodal stimulation on the unaffected side led to improvements. Stimulating both sides of the brain did not lead to improvement. Overall it was found that there were no changes in the activity between the two hemispheres of the brain as a result of the tdcs. This suggests that the improvements in hand and arm function observed in the Jebsen Taylor Test were not due to this type of change in brain activity. In conclusion, tdcs was not able to improve learning with the computer based task that was used for the study, although it was effective at improving the function of the hand and arm when applied to one hemisphere at a time. This is the first study to demonstrate, in chronic stroke survivors, a clear effect of electrode arrangement on tasks that reflect activities of daily living. Brain connectivity being measured with TMS (transcranial magnetic stimulation). What does this mean for stroke survivors? This study suggests that electrode arrangement on the scalp is an important factor in the effectiveness of transcranial direct current stimulation (tdcs) to improve functional arm and hand ability after stroke. This finding may prove important in future study combining tdcs with physiotherapy for arm and hand rehabilitation. stroke.org.uk 3

4 References 1. Dobkin, B. H. (2005). Rehabilitation after stroke. New England Journal of Medicine, 352(16), DOH. National Stroke Strategy Accessed 12/12/ Kleim, J. A. (2011). Neural plasticity and neurorehabilitation: teaching the new brain old tricks. Journal of communication disorders, 44(5), Stagg, C. J., Jayaram, G., Pastor, D., Kincses, Z. T., Matthews, P. M., & Johansen-Berg, H. (2011). Polarity and timing-dependent effects of transcranial direct current stimulation in explicit motor learning. Neuropsychologia, 49(5), Vines, B. W., Cerruti, C., & Schlaug, G. (2008). Dualhemisphere tdcs facilitates greater improvements for healthy subjects non-dominant hand compared to unihemisphere stimulation. BMC neuroscience, 9(1), Mahmoudi, H., Haghighi, A. B., Petramfar, P., Jahanshahi, S., Salehi, Z., & Fregni, F. (2011). Transcranial direct current stimulation: electrode montage in stroke. Disability and rehabilitation, 33(15-16), Bolognini, N., Vallar, G., Casati, C., Latif, L. A., El-Nazer, R., Williams, J.,... & Fregni, F. (2011). Neurophysiological and behavioral effects of tdcs combined with constraintinduced movement therapy in poststroke patients. Neurorehabilitation and neural repair, 25(9), Williams, J. A., Pascual-Leone, A., & Fregni, F. (2010). Interhemispheric modulation induced by cortical stimulation and motor training. Physical Therapy, 90(3), Fleming, M. K., Newham, D. J., & Rothwell, J. C. (2016). Explicit motor sequence learning with the paretic arm after stroke. Disability and Rehabilitation, Zimerman, M., Heise, K. F., Hoppe, J., Cohen, L. G., Gerloff, C., & Hummel, F. C. (2012). Modulation of training by singlesession transcranial direct current stimulation to the intact motor cortex enhances motor skill acquisition of the paretic hand. Stroke, 43(8), Bastani, A., & Jaberzadeh, S. (2012). Does anodal transcranial direct current stimulation enhance excitability of the motor cortex and motor function in healthy individuals and subjects with stroke: a systematic review and metaanalysis. Clinical Neurophysiology, 123(4), Fusco, A., De Angelis, D., Morone, G., Maglione, L., Paolucci, T., Bragoni, M., & Venturiero, V. (2013). The ABC of tdcs: effects of anodal, bilateral and cathodal montages of transcranial direct current stimulation in patients with stroke a pilot study. Stroke research and treatment, O Shea, J., Boudrias, M. H., Stagg, C. J., Bachtiar, V., Kischka, U., Blicher, J. U., & Johansen-Berg, H. (2014). Predicting behavioural response to TDCS in chronic motor stroke. Neuroimage, 85, Boggio, P. S., Nunes, A., Rigonatti, S. P., Nitsche, M. A., Pascual-Leone, A., & Fregni, F. (2007). Repeated sessions of noninvasive brain DC stimulation is associated with motor function improvement in stroke patients. Restorative neurology and neuroscience, 25(2), Can brain stimulation help with relearning movement after stroke?

5 We are the Stroke Association The Stroke Association is the leading stroke charity in the UK. We believe in the power of research to save lives, prevent stroke and ensure that people make the best recovery they can after a stroke. We re here for you. If you d like to know more, please get in touch. Stroke Helpline: Website: stroke.org.uk info@stroke.org.uk From a textphone: Our research programme relies on voluntary donations. Please help us to fund more vital research. Call our Donations line on , or visit stroke.org.uk Together we can conquer stroke Stroke Association, April 2017 Stroke Association is a Company Limited by Guarantee, registered in England and Wales (No 61274). Registered office: Stroke Association House, 240 City Road, London EC1V 2PR. Registered as a Charity in England and Wales (No ) and in Scotland (SC037789). Also registered in Northern Ireland (XT33805) Isle of Man (No 945) and Jersey (NPO 369).